OP0086 ANTIBODIES AGAINST ADVANCED GLYCATION END-PRODUCTS (ANTI-AGE) DISTINGUISH PATIENTS WITH A MORE INFLAMMATORY PROFILE AND WORSE OUTCOME IN SERONEGATIVE RHEUMATOID ARTHRITIS
Authors: T. J. van Wesemael, M. D. van den Beukel, A. T. W. Hoogslag, T. Huizinga, R. Toes, L. A. Trouw, D. van der Woude
Journal: Annals of the Rheumatic Diseases (2022)

Background In rheumatoid arthritis (RA) around two-thirds of patients are autoantibody-positive for rheumatoid factor, anti-citrullinated protein antibodies (ACPA) and/or anti-carbamylated protein antibodies (anti-CarP). The remaining seronegative subgroup of RA is clinically heterogeneous and thus far, biomarkers predicting the disease course in these patients are lacking. Therefore, we set out to investigate the value of a new/different autoantibody in rheumatoid arthritis directed against advanced glycation end-product (AGE) modified proteins (anti-AGE). AGEs are a marker of oxidative stress, and anti-AGE have been described in multiple diseases including diabetes, and hypertension. Objectives To investigate the prevalence of anti-AGE in RA and non-RA arthritis patients, as well as their association with clinical parameters and disease outcome in RA. Methods In 648 RA patients and 538 non-RA arthritis patients from the Leiden Early Arthritis Clinic anti-AGE IgG antibody levels were measured using an in-house fetal calf serum (FCS) ELISA based assay using native FCS as control. The cutoff for positivity was set as the mean optical density plus two times the standard deviation of 80 healthy controls. Radiological progression was measured with the with Sharp van der Heijde score (SHS) on yearly basis and the association with anti-AGE was assessed with a multivariate normal regression model. Results Anti-AGE was found in 299 (46%) of RA patients versus 163 (30%) of non-RA arthritis patients. Interestingly, 67 (34%) of completely seronegative (RF-, ACPA- and anti-CarP-negative) RA patients were positive for anti-AGE. Within RA, anti-AGE-positive patients had significantly higher ESR (median anti-AGE-positive: 38, anti-AGE-negative: 32, p&lt;0.001) and CRP (median anti-AGE-positive: 19, anti-AGE-negative: 17, p&lt;0.001), indicating an more inflammatory profile in these patients. Radiographic progression, was significantly higher in anti-AGE+ patients (Figure 1A, B=1.05, p&lt;0.001). Since ACPA and anti-CarP (in ACPA-patients) are associated with radiological progression, the analysis was first stratified for ACPA-status. In the anti-AGE+ACPA- patients a significant association with SHS was found (Figure 1B: B=1.04, P&lt;0.001), indicating that anti-AGE is associated with radiological progression in ACPA-negative patients. Next, the ACPA-negative stratum was also stratified for anti-CarP. Interestingly, SHS was significantly higher in all anti-AGE+ groups compared to the autoantibody-negative group. Conclusion Almost half of the RA patients are anti-AGE positive including a substantial part of otherwise completely seronegative RA patients. Anti-AGE antibodies are associated with inflammatory parameters and radiologic progression in seronegative RA patients. Therefore, although these autoantibodies are not specific for RA, anti-AGE could potentially identify patients with a more inflammatory phenotype and more severe disease outcome in “classic” autoantibody-negative RA patients. Disclosure of Interests None declared.